Gastric Cancer, Non-Small Cell Lung Cancer (NSCLC), Pancreatic Cancer, Pancreatic Ductal Adenocarcinoma (PDAC), Solid Tumors
Conditions
Keywords
ADC, TOP1 inhibitor, Gastric Cancer, Gastroesophageal junction cancer, Non-Small Cell Lung Cancer, Pancreatic Cancer, Solid Tumors
Brief summary
The PROCEADE PanTumor study aims to investigate M9140 in multiple tumor types which express carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and it is therefore designed as a matrix study. This study aims to assess the antitumor activity, tolerability, safety, and pharmacokinetics (PK) of M9140 as monotherapy or in combination treatments in adult participants with locally advanced/metastatic CEACAM5 expressing tumors. There will be 3 substudies under this Master Protocol that may be conducted in parallel. * PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open-Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants with Advanced Gastric Cancer (Substudy GC); * PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open-Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants with Advanced Non-Small Cell Lung Cancer (Substudy NSCLC); * PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants With Advanced Pancreatic Cancer (Substudy PDAC).
Detailed description
The study follows a master protocol concept with several separate substudies in specific indications. * Substudy GC: The study duration per participant is on an average approximately 10 months. This includes a 28-day Screening period, infusion (approximately 1 hour) on Day 1 of every cycle, and Safety Follow-up Visit 30 (± 3) days after the last dose of M9140. * Substudy NSCLC: Study duration per participant is approximately 12 months. This includes a 28-day Screening period, infusion (approximately 1 hour) on Day 1 of every cycle, and Safety Follow-up Visit 30 (± 3) days after the last dose of M9140. * Substudy PDAC: Study duration per participant is on an average approximately 8 months. This includes a 28-day Screening period, infusion (approximately 1 hour) on Day 1 of every cycle, and Safety Follow-up Visit 30 (±3) days after the last dose of M9140.
Interventions
DRUGM9140
All participants will receive 2.8 milligram per kilogram (mg/kg) M9140 intravenously (i.v.) every 3 weeks (q3w) on Day 1 of consecutive 21-day cycles.
Sponsors
EMD Serono Research & Development Institute, Inc.
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants are capable of signing informed consent as defined in protocol * Eastern Cooperative Oncology Group Performance Status (ECOG PS) below or equal to 1 * Participants with adequate hematologic, hepatic and renal function as defined in protocol * Participant must have at least 1 lesion that is measurable using RECIST v1.1. * Other protocol defined inclusion criteria could apply Substudy GC: * Participants in Part A and Part B with documented histopathological diagnosis of advanced or metastatic, HER2 negative, gastric or GEJ (with an epicenter 2 centimeter (cm) proximal or distal to the GEJ) adenocarcinoma, who were intolerant/refractory to or progressed after systemic therapies for the advanced/metastatic stage that must have included (provided there is no medical contraindication and these agents are locally approved and available) a fluoropyrimidine and a platinum agent and an Immune checkpoint inhibitors (ICI) for participants with a known microsatellite instability-high (MSI-H) status or participants whose tumor express PD-L1 with a CPS greater than or equal (\>=) 1 * Participants must have received and progressed (according to RECIST 1.1) on at least 1 line of therapy for the treatment of advanced/metastatic disease but no more than 2 * Participants in Part A with CEACAM5high GC/GEJC (defined as IHC \>= 2+ staining in \>= 50% of tumor cells) * Participants in Part B with CEACAM5low GC/GEJC (defined as IHC \>= 2+ staining in less than (\<) 50% of tumor cells) * Other protocol defined inclusion criteria could apply Substudy NSCLC: * Participants in Part A and Part B with histologically or cytologically documented advanced (Stage III not eligible for resection or curative radiation) or metastatic NSCLC with or without driver genomic alterations * Participants must have been intolerant/refractory to or progressed after systemic therapies for the advanced/metastatic stage * Participants must have received and progressed (according to RECIST 1.1) on at least 1 line of therapy for the treatment of advanced/metastatic disease but no more than 3 * Participants who received a platinum-containing regimen or a targeted therapy as (neo)-adjuvant therapy for early-stage disease, if relapse or metastases occurred during or within 3 months after regimen completion, are considered to have received a line of treatment in the advanced setting * Participants in Part A with CEACAM5 high-expressing EGFR tumors (including participants with any driver genomic alterations other than EGFR mutations * Participants in Part B with CEACAM5 high known EGFR mutated tumors as assessed according to local clinical practice * Other protocol defined inclusion criteria could apply Substudy PDAC: * Participants with histologically or cytologically confirmed advanced or metastatic PDAC, who were intolerant/refractory to or progressed after systemic therapies for the advanced metastatic stage that must have included (provided there is no medical contraindications, and these agents are locally approved and available; FOLFIRINOX regimen or NALIRIFNOX regimen or Nab-paclitaxel/gemcitabine regimen * Participants must have received and progressed (according to RECIST 1.1) on at least one 1 line of therapy for the treatment of advanced/metastatic disease but no more than 2 * All participants will be screened using an IHC test to define CEACAM5 expression. Only participants with CEACAM5high expressing tumors will be eligible * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Participant has a history of malignancy within 3 years before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, benign prostate neoplasm/hypertropia, or malignancy that in the opinion of the Investigator, with concurrence with the Sponsor's Medical Monitor, is considered cured with minimal risk of recurrence within 3 years) * Participants with known brain metastases, except those meeting the following criteria: Brain metastases that have been treated locally and are clinically stable for at least 4 weeks prior to the start of treatment; No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) * Participants with diarrhea (liquid stool) or ileus Grade \> 1 * Participants with active chronic inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease, intestinal perforation) and/or bowel obstruction * Cardiac arrhythmia, unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] \>= II) or a coronary revascularization procedure within 180 days of study entry. Calculated QTc average (using the Fridericia correction calculation) of \> 470 milliseconds (ms) * Cerebrovascular accident/stroke (\< 6 months prior to enrollment) * Other protocol defined
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Substudies GC/NSCLC/PDAC: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigators | Time from first study treatment to (planned) final assessment at approximately 48 months |
Secondary
| Measure | Time frame |
|---|---|
| Substudies GC/NSCLC/PDAC: Number of Participants with Adverse Events (AEs) and Treatment Related AEs | Time from first study treatment to (planned) final assessment at approximately 48 months |
| Substudies GC/NSCLC/PDAC: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigators | Time from first study treatment to (planned) final assessment at approximately 48 months |
| Substudies GC/NSCLC/PDAC: Number of Participants with Disease Control | At Week 12 |
| Substudies GC/NSCLC/PDAC: Time to Response according to RECIST v1.1 as Assessed by Investigators | Time from first study treatment to (planned) final assessment at approximately 48 months |
| Substudies GC/NSCLC/PDAC: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigators | Time from first study treatment throughout the study duration until progressive disease or death due to any cause, whichever occur first, approximately 48 months |
| Substudies GC/ NSCLC/ PDAC: Pharmacokinetic (PK) Plasma Concentrations of M9140 | Cycle (C) 1 Day (D) 1 to C3D15, C4D1 and from C8D1 every 4 cycles on D1 until treatment discontinuation (each cycle is of 21 days), assessed up to approximately 12 months |
| Substudies GC/NSCLC/PDAC: Number of Participants with Anti-Drug Antibodies (ADA) Against M9140 | Predose (C1D1, C3D1, C8D1) and end of study intervention, assessed up to approximately 12 months |
| Substudy GC: CEACAM5 expression in tumor | Day 1 |
Countries
Australia, Austria, China, France, Germany, Italy, Japan, South Korea, Spain, United States
Contacts
STUDY_DIRECTORMedical Responsible
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Outcome results
None listed